Bone marrow (bursal-equivalent)-derived thymus-independent B lymphocytes mediate the humoral immune response. The B cell differentiation pathway can be divided into two stages based upon contact with antigen. Unprimed B lymphocytes in the adult mouse are derived from virgin B cells which develop ultimately from multipotent stem cells. Primed (memory) B cells are generated as a result of antigenic stimulation. While the unprimed B lymphocytes acting as IgM antibody forming cell progenitors and the memory B cells giving an IgG antibody forming cell response have been well characterized, the identify of the precursors of the memory cell is unknown. The physical characteristics of the precursor of the memory B lymphocyte will be determined and the cells isolated by a battery of cell separation procedures, including buoyant density centrifugation, cell electrophoresis, and sedimentation velocity separation. Cell surface immunoglobulin isotype, differentiation antigens, and non-immunoglobulin surface receptors will also be used to characterize the memory B cell precursor. The various B cell subpopulations separated by these methods will be assayed for their ability to generate a memory state in response to antigenic priming and subsequently mount a memory response following secondary challenge. A long-term adoptive assay based upon the use of allotype congenic mice will allow both host survival over the long duration required for the generation of a stable memory state and the enumeration of a donor IgG response in the presence of a significant host contribution. Additional parameters characterizing the memory cell precursor will be investigated, including kinetics of memory generation, turnover rate of the precursor cell, and relationship between the memory precursors and the cells giving a primary antibody response to the memory-generating immunization.